C-type natriuretic peptide inhibits rat mesangial cell proliferation by a phosphorylation-dependent mechanism.
We studied the effects of C-type natriuretic peptide (CNP) on rat cultured mesangial cell proliferation. (1) Exposure to CNP (10 nM-1 microM for 72 h) inhibited [3H]thymidine incorporation into mesangial cells in a concentration-dependent manner. Atrial natriuretic peptide (1 nM-1 microM), a peptide related to CNP, also decreased [3H]thymidine incorporation into these cells in a concentration-dependent manner. (2) Both CNP (10 nM- microM) and atrial natriuretic peptide (10 nM-1 microM) also decreased mesangial cell number. (3) The cyclic GMP analog, 8-bromo-cyclic GMP (100 microM and 1 microM), mimicked the inhibitory effects of CNP and atrial natriuretic peptide on [3H]thymidine incorporation into mesangial cells, whereas inhibitors of protein kinase C, protein kinase A, and protein kinase G reduced the effect of both natriuretic peptides. Moreover, the phosphatase inhibitor, calyculin A, increased [3H]thymidine incorporation into mesangial cells. (4) CNP and atrial natriuretic peptide decreased interleukin-1-, interleukin-6-, platelet derived growth factor-, angiotensin II-induced [3H]thymidine incorporation into mesangial cells. These results suggest that CNP exerts inhibitory effects on mesangial cell proliferation and that this effects depend on protein phosphorylation pathways.
Segawa
K
K
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Fukuoka, Japan.
Minami
K
K
Jimi
N
N
Nakashima
Y
Y
Shigematsu
A
A
D000804:Angiotensin II; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008387:Marine Toxins; D020098:Natriuretic Peptide, C-Type; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011506:Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D008387:Marine Toxins; D010080:Oxazoles; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D000804:Angiotensin II; D020098:Natriuretic Peptide, C-Type; C016276:8-bromocyclic GMP; C059041:calyculin A; D009320:Atrial Natriuretic Factor; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D006152:Cyclic GMP; D013936:Thymidine